On June 5, 2022 NANOBIOTIX (Euronext : NANO –– Nasdaq: NBTX – the ‘‘Company’’), a late-clinical stage biotechnology company pioneering physics-based approaches to expand treatment possibilities for patients with cancer, reported the reporting of new data at the 2022 Annual Meeting of the American Society for Clinical Oncology (ASCO) (Free ASCO Whitepaper) featuring potential first-in-class radioenhancer NBTXR3 in combination with concurrent chemoradiation for the treatment of head and neck cancer and rectal cancer (Press release, Nanobiotix, JUN 5, 2022, View Source [SID1234615581]). Nanobiotix also presented a trial-in-progress poster on the study design of the Company’s ongoing pivotal phase 3 study, NANORAY-312, evaluating NBTXR3 as a single agent activated by radiotherapy for the treatment of elderly and frail patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who are ineligible for platinum-based chemotherapy (cisplatin).

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In view of the Company’s strategy for development of NBTXR3 as a product candidate that can integrate across solid tumor indications along with major treatment modalities within each indication, starting with head and neck cancer, the company believes these new data add support for the radioenhancer in combination with chemoradiation and as a neoadjuvant (preoperative) therapy with the potential to improve surgical outcomes. "Revolutionizing treatment outcomes for millions of patients with cancer will require integration of NBTXR3 across solid tumor indications, treatment modalities, and lines of therapy where radiation is a part of the treatment regimen—starting with head and neck cancer," said Laurent Levy, co-founder and chairman of the executive board at Nanobiotix. "Taken together with the clinical data we have already produced for NBTXR3 as a single agent activated by radiotherapy and as a combination agent with anti-PD-1, we view the new chemoradiation data presented at ASCO (Free ASCO Whitepaper) as critical validation of NBTXR3’s feasibility across the standard of care. As we continue to prioritize our ongoing pivotal phase 3 study for elderly and frail patients with locally advanced head and neck squamous cell carcinoma, our aim is to build a comprehensive approach to the treatment of patients with locally advanced head and neck cancer that will serve as a model for our radioenhancer in other indications."

A Comprehensive Approach to Locally Advanced Head and Neck Cancer Inclusive of Chemoradiation

Most cisplatin-eligible patients with LA-HNSCC receive multimodal therapy including high dose concurrent chemoradiation (CCRT) as the standard of care. While CCRT has shown to improve local control and extend survival, the toxicity of high dose cisplatin creates challenges. These challenges appear both in terms of compliance with the treatment regimen for patients undergoing therapy that can impair efficacy, and in terms of the patients’ quality of life after treatment. Although changes to the treatment protocol have been explored in randomized studies to reduce toxicity and improve compliance, reduction in toxicity has also led to reduction in efficacy.

These patients need innovative new therapeutic options that do not create additional burden in their administration, do not add combined toxicity to radiotherapy and chemotherapy, and have the potential to improve survival.

A Phase 1b/2 Study Evaluating NBTXR3 in Combination with Concurrent Chemoradiation for Patients with Locally Advanced or Recurrent Head and Neck Squamous Cell Carcinoma

This study, sponsored, executed, and reported by former Nanobiotix collaborator in Asia, PharmaEngine, Inc. (PEI), sought to evaluate the safety and feasibility of NBTXR3 intratumoral injection when added to low-dose weekly cisplatin-containing CCRT for patients with locally advanced or recurrent head and neck squamous cell carcinoma. The study also aimed to establish the recommended phase 2 dose (RP2D), however the RP2D was not determined due to stoppage of the phase 1b part of the trial resulting from the conclusion of the collaboration between PEI and Nanobiotix in 2021.

Adult patients with T3-4 LA-HNSCC suitable for cisplatin were eligible for the study and 12 such patients were enrolled. These patients received a single intratumoral injection of NBTXR3, followed by a low-dose weekly regimen of CCRT. All 12 patients were deemed evaluable and all had stage 4 locally advanced disease.

Of these evaluable patients, 3, 6, and 3 patients received NBTXR3 at the 5%, 10%, and 15% dose levels, respectively. No serious adverse events (SAEs) inconsistent with what would normally be expected from a low-dose CCRT regimen were observed. Dose-limiting toxicities of grade 3 increased ALT and grade 3 increased AST were observed in one patient at the 10% dose level. Common Grade 3 adverse events (AEs) observed across dose levels were stomatitis, decreased WBC, decreased appetite, decreased neutrophil count, and leukopenia. One patient experienced grade 4 hyponatremia.

Preliminary efficacy results showed a disease control rate of 100%, with an overall response rate of 58.3% according to RECIST 1.1. The study concluded that adding a single intratumoral injection of NBTXR3 to weekly low dose cisplatin-containing CCRT was feasible and had a favorable safety profile for patients with LA-HNSCC.

Strengthening Support for NBTXR3 in Combination with Chemoradiation in the Preoperative Setting

Colorectal cancer (CRC) is the third most common cancer indication worldwide and the second leading cause of cancer-related death in the United States. One-third of CRCs appear in the rectum. For patients with locally advanced rectal cancer (LARC), combined modality therapy with neoadjuvant CCRT, followed by total mesorectal excision (TME; surgery), followed by adjuvant (post-operative) systemic chemotherapy is the current standard of care. The aim of the neoadjuvant portion of the treatment regimen is to control and downstage the disease to allow for R0 TME (surgical removal with a negative margin in which no gross or microscopic tumor remains in the primary tumor bed), as clinical studies have shown a positive correlation between improved cancer-specific survival and R0 TME. While outcomes have improved, patients are still faced with a highly toxic treatment regimen that can lead to a lack of compliance which may hamper efficacy, along with deteriorated quality of life after treatment.

Innovation with the potential to improve the rate of R0 resection without adding toxicity is an urgent need for this patient population.

A Phase 1b/2 Study Evaluating NBTXR3 in Combination with Concurrent Chemoradiation in the Neoadjuvant Setting for Patients with Locally Advanced or Unresectable Rectal Cancer

This study, sponsored, executed, and presented by PEI, sought to evaluate safety, feasibility, and early signs of efficacy for neoadjuvant NBTXR3 combined with CCRT followed by surgery for patients with locally advanced or unresectable rectal cancer. The study established the recommended phase 2 dose of NBTXR3 at 22% of gross tumor volume, however the phase 2 part of the trial was stopped as a result of the conclusion of the collaboration between PEI and Nanobiotix in 2021. Adult and older patients with T3-T4 locally advanced or unresectable rectal cancer suitable for chemoradiation were eligible for the study and 32 such patients were enrolled. These patients received a single intratumoral injection of NBTXR3, followed by a weekly regimen of CCRT. 31 of 32 patients were deemed evaluable and none of the evaluable patients had tumors eligible for surgery at the time of diagnosis.

Of the 31 evaluable patients, 6, 4, 3, and 18 patients received NBTXR3 at the 5%, 10%, 15%, and 22% dose levels, respectively. No NBTXR3-related SAEs or grade ≥ 3 AEs were observed. The most frequently reported AEs were grade 1 or 2 decreased WBC, diarrhea, increased CRP, UTI, and decreased lymphocyte count which were all consistent with what would normally be expected from CCRT.

Preliminary efficacy results showed a disease control rate of 100%, with an overall response rate of 35.5% according to RECIST 1.1. Pathological tumor downstaging was observed in 14 of 31 patients after therapy, 25 patients underwent surgery, and 96% of those patients achieved R0 surgical margins. Pathological complete response was observed in 20% of the patients who received surgery. The study concluded that a single intratumoral injection of NBTXR3 in combination with CCRT is feasible and has a favorable safety profile in the neoadjuvant setting for patients with locally advanced or unresectable rectal adenocarcinoma.

***

About NBTXR3

NBTXR3 is a novel, potentially first-in-class oncology product composed of functionalized hafnium oxide nanoparticles administered via one-time intratumoral injection and activated by radiotherapy. The product candidate’s physical mechanism of action (MoA) is designed to induce significant tumor cell death in the injected tumor when activated by radiotherapy, subsequently triggering adaptive immune response and long-term anti-cancer memory. Given the physical MoA, Nanobiotix believes that NBTXR3 could be scalable across any solid tumor that can be treated with radiotherapy and across any therapeutic combination, particularly immune checkpoint inhibitors.

On June 5, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported that updated efficacy and safety results from the teclistamab Phase 1/2 MajesTEC-1 study.1 Teclistamab is an investigational, off-the-shelf, T-cell redirecting bispecific antibody targeting B-cell maturation antigen (BCMA), which is being studied in patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Johnson & Johnson, JUN 5, 2022, View Source [SID1234615579]).1 The data were featured as part of an oral session during the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. Applications seeking approval of teclistamab are currently under health authority review in the United States (U.S.) and Europe.

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The multicohort, open-label, Phase 1/2 MajesTEC-1 study is investigating the safety and efficacy of teclistamab in patients with RRMM who received at least three prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody.3 As of March 2022, 165 patients were treated with teclistamab at the recommended subcutaneous (SC) Phase 2 dose (RP2D) of 1.5 mg/kg preceded by step-up doses of 0.06 mg/kg and 0.3 mg/kg across both Phase 1 (NCT03145181) and Phase 2 (NCT04557098) of the study.1

Longer Follow-up from MajesTEC-1 Study in Patients with Triple Class Exposed Multiple Myeloma (Abstract #8007)

At a median follow-up of 14.1 months (range, 0.26-24.4), an overall response rate (ORR) of 63 percent (95 percent Confidence Interval [CI], range, 55.2-70.4) was observed in patients with triple class exposed multiple myeloma, with a complete response (CR) or better achieved in 39.4 percent of patients.1 Study participants had three or more prior lines of therapy, with a median of five prior lines, including a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 antibody​.1 The majority of patients were triple-class refractory and/or refractory to their last line of treatment.1 Although response duration data are not mature, the median duration of response at this time is 18.4 months and has not been reached in patients who achieved a CR or better (95 percent CI, 14.9 not estimable).1 This suggests responses to teclistamab were durable and deepened over time.1 The medium progression-free survival (PFS) was 11.3 months (95 percent CI, 8.8–17.1).1 Adverse events (AEs) were low-grade for the most part and manageable with no new safety signals seen.1

These results from the MajesTEC-1 study were also simultaneously published online in The New England Journal of Medicine.2

"The longer term results from the MajesTEC-1 study suggest that patients are able to achieve deep and durable responses when treated with teclistamab," said Maria-Victoria Mateos, M.D., Ph.D., Consultant Physician in Haematology, University Hospital of Salamanca.* "These encouraging data reinforce the potential of teclistamab as a monotherapy for eligible patients with heavily pretreated multiple myeloma, in need of new treatment options."

No new safety signals were observed with longer follow-up.1 In 14.1 month follow-up data presented, the most common grade 3/4 haematologic AEs were neutropenia (64.2 percent); anaemia (37 percent); lymphopenia (32.7 percent) and thrombocytopenia (21.2 percent).1 Infections occurred in 76.4 percent of patients (44.8 percent grade 3/4).1 The most common nonhaematologic AE was cytokine release syndrome (CRS), all of which were grade 1/2 except for one transient grade 3 CRS (72.1 percent all grade).1 The median time to CRS onset was two days (range, 1-6) and median duration was two days (range, 1-9).1 There were five treatment-related deaths, and dose reductions and discontinuations due to AEs were infrequent.1

First Results from Cohort C of the MajesTEC-1 Study of Teclistamab in Patients with RRMM with Prior Exposure to BCMA Targeted Treatment (Abstract #8013)

Initial results were also presented from Cohort C of the MajesTEC-1 study evaluating teclistamab in the treatment of patients with RRMM who had previously been exposed to an anti-BCMA treatment.4 These patients had received a median of six prior lines of therapy, most (85 percent) were triple-class refractory and 35 percent were penta-drug refractory.4 The use of teclistamab following prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy and/or an antibody drug conjugate (ADC) (e.g., belantamab mafodotin) targeting BCMA resulted in a promising response rate in patients with heavily pretreated RRMM.4 At a median follow-up of 12.5 months (range, 0.7-14.4), the ORR was 52.5 percent (95 percent CI, 36.1-68.5) among 40 patients who received teclistamab in Cohort C.4 Responses to teclistamab occurred early and deepened over time, with comparable response rates in patients previously treated with an ADC and/or CAR-T.4

A tolerable side-effect profile was observed in patients previously treated with anti-BCMA treatment, with no dose reductions or discontinuations due to AEs.4 The safety profile for Cohort C was comparable with that observed in BCMA treatment-naive patients, with no new safety signals.4 In 12.5 month follow-up data, 26 patients (65 percent; 30 percent grade 3/4) had infections.4 The most common AEs (n=40) were CRS (65 percent any grade), with a median time to CRS onset and duration of two days (range, 2-6) and two days (range, 1-4) respectively.4 Cytopenias (grade 3/4) were noted as follows; neutropenia (62.5 percent); thrombocytopenia (30 percent); anaemia (35 percent); and lymphopenia (42.5 percent).4

"Patients with relapsed or refractory multiple myeloma have limited treatment options and only 30 percent will be able to achieve a response using conventional therapies," said Edmond Chan MBChB M.D. (Res), EMEA Therapeutic Area Lead Haematology, Janssen-Cilag Limited. "While unmet needs remain, we continue to be dedicated to developing innovative treatment approaches that improve outcomes for people living with multiple myeloma, at all stages of the disease."

Initial Patient-Reported Health-Related Quality of Life (HRQoL) Outcomes in Patients with RRMM Treated with Teclistamab (Abstract #8033)

Initial results from an analysis of patient-reported health-related quality of life (HRQoL) outcomes following treatment with teclistamab were also shared in a poster session.5 The study analysed patient-reported assessments of quality of life metrics among patients in the MajesTEC-1 trial who had received their first treatment dose by March 18, 2021.5 The metrics analysed include function (physical, role, emotional, cognitive, social); symptoms (fatigue, nausea/vomiting, pain, appetite loss, constipation, diarrhoea); and generic health (mobility, self-care, usual activities, pain/discomfort, anxiety/depression).5 Over 80 percent of the 110 patients included in the patient-reported outcomes (PRO) analysis noted meaningful improvement (percentages of patients with clinically meaningful change from baseline (EORTC QLQ-C30 scales: ≥10 points)) in at least one of the symptom scales.5 Reduction in pain scores occurred as early as cycle two.5 At the moment, no meaningful improvement was observed in the scales for physical functioning and fatigue.5 These initial PRO results complement recent clinical data and support teclistamab as a potential off-the-shelf, T-cell redirecting therapy for patients with RRMM.5

As of September 7, 2021, median duration of treatment was 5.7 months and median follow-up was 7.8 months.5 Global health​ status scores significantly improved from baseline (95 percent CIs for least squares mean change did not cross 0) at cycles four, six, and eight; emotional functioning significantly improved at all time points.5 PRO assessments included European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 item (EORTC QLQ-C30).5 PROs were assessed on day one of each treatment cycle (28 days per cycle).5 Additional follow-up is needed to assess the full benefit of meaningful improvement in functional outcomes.5

"The updated data presented at ASCO (Free ASCO Whitepaper) support the ongoing evaluation of teclistamab for the treatment of relapsed or refractory multiple myeloma," said Yusri Elsayed, M.D., M.HSc., Ph.D., Vice President, Disease Area Leader, Hematologic Malignancies, Janssen Research & Development, LLC. "These results underscore our ongoing commitment to address the unmet need for new therapeutic options and our effort to bring forward novel treatments for multiple myeloma patients in the near future."

#ENDS#

About Teclistamab

Teclistamab is an investigational, fully humanised IgG4, T-cell redirecting, bispecific antibody targeting both BCMA and CD3, on T-cells.1 BCMA is expressed at high levels on multiple myeloma cells.6,7,8,9,10 Teclistamab redirects CD3-positive T-cells to BCMA-expressing myeloma cells to induce killing of tumor cells.11

Teclistamab is currently being evaluated in several monotherapy and combination studies.3,12,13,14,15 In 2020, the European Commission (EC) and the U.S. Food and Drug Administration (FDA) each granted teclistamab Orphan Drug Designation for the treatment of multiple myeloma. In January 2021 and June 2021, teclistamab received a PRIority MEdicines (PRIME) designation by the European Medicines Agency (EMA) and Breakthrough Therapy Designation (BTD) by the FDA, respectively. PRIME offers enhanced interaction and early dialogue to optimise drug development plans and speed up evaluation of cutting-edge, scientific advances that target a high unmet medical need.16 The U.S. FDA grants BTD to expedite the development and regulatory review of an investigational medicine that is intended to treat a serious or life-threatening condition and is based on preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy.17 In December 2021, Janssen submitted a Biologics License Application (BLA) to the FDA seeking approval of teclistamab for the treatment of patients with RRMM; a marketing authorisation application (MAA) was submitted to the EMA for teclistamab approval in January 2022.

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.18 In multiple myeloma, cancerous plasma cells change and grow out of control.18 In Europe, more than 50,900 people were diagnosed with multiple myeloma in 2020, and more than 32,500 patients died.19 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms, which can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels or kidney failure.20

On June 5, 2022 Agendia, Inc., a commercial-stage company focused on improving outcomes for breast cancer patients worldwide by providing physicians and patients with next-generation diagnostic and information solutions to inform optimized treatment decision-making, reported it will present seven posters derived from the company’s FLEX Trial, the real-world, multicenter, prospective, observational breast cancer study at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) 2022 (Press release, Agendia, JUN 5, 2022, View Source [SID1234615578]).

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One of Agendia’s posters, selected for the oral discussion session, titled Whole transcriptomic analysis of HR+ breast cancer in Black women classified as basal-type by BluePrint [Reid, S., et al.], will present findings from a racially-diverse cohort and resulting transcriptomic analyses suggesting hormone receptor-positive (HR+)/Basal tumors are biologically similar to triple-negative breast cancer (TNBC) tumors, regardless of race, demonstrating the importance of subtyping a tumor’s biology to determine optimal treatment course. BluePrint also identified racial disparities in the proportion of HR+/Basal tumors, showing a near doubling of such tumors among Black women, underscoring the need for diverse representation in clinical trials, a hallmark of the FLEX Trial.

"Leveraging the BluePrint assay, we are able to uncover new gene expression insights for HR+/Basal breast cancer tumors, which traditionally are more aggressive, higher grade, and disproportionally impact Black women compared to White women," said Sonya Reid, MD, MPH, Department of Medicine, Vanderbilt University Medical Center. "The FLEX Trial’s robust collection of diverse patient genomic profiles uniquely allows for sub-studies analyses like these to take place, helping researchers better support their patients from all racial and ethnic backgrounds with further classification of breast cancer tumors."

These data build on findings presented at San Antonio Breast Cancer Symposium 2021, also authored by Dr. Reid, that showed MammaPrint and BluePrint more robustly identify differences in more aggressive breast cancers in Black and White women beyond clinical factors, highlighting the fundamental importance of genomic classification and personalized treatment planning.

In addition, Agendia will present several sub-studies highlighting the FLEX Trial’s approach to cancer research by accelerating impactful data generation, aimed at redefining cancer care. The company believes this patient-centric design and national network of participating sites backed by Agendia will allow its investigator-initiated sub-studies to produce important results with the potential to drive science forward, like those being shared at ASCO (Free ASCO Whitepaper) 2022:

Clinical implications for patients with discordant Oncotype and MammaPrint results [Socoteanu, M., et al.] recalls findings from the IMPACT trial, which demonstrated MammaPrint and BluePrint inform treatment planning and increase physician confidence. In an effort to examine consistency among genomic tests, researchers analyzed therapy implications for patients who received both results from MammaPrint and BluePrint as well as OncotypeDx within the FLEX Trial:
Of 722 patients, 49% were observed to have discordant results with the potential of negative clinical impact. This includes 27% who may be undertreated, 6% potentially overtreated, and 10% who may not be given the option to decrease endocrine therapy to two years based on MammaPrint Ultra Low genomic risk assessment. Of 114 concordant MammaPrint High Risk tumors, 14% were genomically classified as Basal, and likely require more aggressive chemo than typically used in estrogen receptor-positive (ER+) breast cancers.
Together, these analyses showed more than half the patients in this cohort were at potential risk for undertreatment or overtreatment, had they received an OncotypeDx test as a standalone test. Discordance between OncotypeDx Recurrence Scores and MammaPrint with BluePrint results, most often yields the potential for undertreatment if the Recurrence Score is relied upon for treatment decision-making, putting a significant amount of risk on the patient since undertreatment may result in an incurable metastatic recurrence.
Whole transcriptome analysis of tumors with discordant Oncotype and MammaPrint results in the FLEX trial [Socoteanu, M., et al.] also looked at the differences in quality of results from OncotypeDx Recurrence Scores in comparison to MammaPrint results, this time by evaluating the genomic diversity within each test’s classification. The analysis found a high amount of genomic diversity within the OncotypeDx Recurrence Score Intermediate group, while conversely showing MammaPrint further classifies cases into more genomically rich and distinct categories, allowing for more precise treatment pathways based on the individual tumor.
Investigation of a genomic signature for transcription factor MAF gene amplification and lack of bisphosphonate benefit in early breast cancer [Nasrazadani, A. et al.] provides whole transcriptome analyses suggesting breast cancer tumors with mesenchymal aponeurotic fibrosarcoma (MAF) gene amplifications – a biomarker associated with shortened survival and lack of bisphosphate benefit when related to bone metastases in breast cancer – may be identified by a unique gene expression pattern. In this study, researchers used the MammaPrint/BluePrint platform to identify a set of 57 genes that could potentially predict MAF amplification status which could enable a woman’s care team to potentially anticipate a lack of benefit from adjuvant bisphosphonate treatment. Additionally, these results show mining the complete genome more thoroughly provides expanded insights and can shed light on new biomarkers previously unknown.
Distribution of breast cancer molecular subtypes within receptor classifications: Lessons from the I-SPY2 trial and FLEX Registry [Cha, J., et al.] proposes that the breast cancer research community drive science forward and work with the NCI’s Surveillance, Epidemiology, and End Results (SEER) Program to update its immunohistochemical (IHC) labels to avoid overlap with molecular subtype nomenclature and incorporate more modern classifications when available. Study results show the SEER Program database using IHC labels is not accurately identifying genomic subtypes via its annotations. In fact, the categorizations in the population-based registry were discordant with MammaPrint and BluePrint results in 52% of I-SPY2 Trial cases and 43% of FLEX Trial cases, emphasizing the growing importance of molecular subtyping to inform treatment and epidemiological research.
Defining transcriptomic profiles of early-stage mucinous breast cancers: A FLEX sub study [Sivapiragasam, A., et al.] revealed although mucinous breast cancer (MuBC), a rare subtype of invasive ductal carcinoma (IDC) accounts for less than 2% of all breast cancers, it often is expected to have low clinical risk and a favorable prognosis, however new genomic testing showed half of the patients observed in the study were in fact classified as MammaPrint High Risk. Through the examination of transcriptomic profiles, the findings demonstrated MammaPrint Low Risk MuBC is biologically different from MammaPrint Low Risk IDC providing new evidence as to why there are more favorable prognoses. Results also indicated MammaPrint High Risk MuBC and High Risk IDCs are highly genomically similar and could benefit from chemotherapy, providing additional clarity to guide specific treatment among these breast cancer subtypes.
FLEX, the 30,000 breast cancer transcriptome project: A platform for early breast cancer research using full-genome arrays paired with clinical data [Ma, C., et al.] shares data from the 38 investigator-initiated sub-studies – including five investigating racial disparities – approved within the FLEX Real World Evidence Trial (NCT03053193). Since the trial’s inception in 2017, FLEX has enrolled 10,000 patients at over 109 sites with a diverse data set designed to meet the needs of historically under-represented patients with breast cancer.
"These new findings presented at ASCO (Free ASCO Whitepaper) 2022 show the breadth of the FLEX research platform to identify and evaluate the many different complexities of a breast cancer biology at diagnosis that may facilitate more precise and individualized treatment recommendations," said William Audeh, MD, Chief Medical Officer at Agendia. "Agendia’s commitment to expanding our understanding of breast cancer to improve outcomes for women with breast cancer is astounding, exemplified by the FLEX Real World Evidence Trial. FLEX has the significant potential to broaden the application of genomic information through assays such as MammaPrint, BluePrint, and new proprietary Agendia signatures, which could lead to practice-changing models within breast cancer care aimed at improved outcomes for women with breast cancer."

On June 5, 2022 InnoCare Pharma (HKEX: 09969), a leading biotech company, reported that Professor Zhanguo Li, the leading PI, has presented latest data of BTK inhibitor orelabrutinib for the treatment of Systemic Lupus Erythematosus (SLE) at the just-concluded EULAR 2022 European Congress of Rheumatology (Press release, InnoCare Pharma, JUN 5, 2022, View Source [SID1234615577]). The abstract was selected as late-breaking oral presentation.

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Late-breaking Oral Presentation:

Orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK), for the treatment of SLE: results of a randomized, double-blind, placebo-controlled, phase Ib/IIa dose-finding study
Abstract Number: LB0005

The study is aimed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), preliminary efficacy and biomarkers of orelabrutinib in patients with mild to moderate SLE who received standard of care therapy.

The study randomized 60 patients with 55 patients who completed 12-week treatment. Baseline disease characteristics were generally balanced across treatment groups. Orelabrutinib was generally well tolerated in patients with SLE.

The plasma exposure of orelabrutinib (AUC and Cmax) was proportionally increased with doses. Nearly complete BTK occupancy was achieved at all dose levels, and the occupancy lasted for 24 hours.

In all evaluable patients, the SLE Response Index (SRI)-4 response rates at week 12 were 50.0%(7/14), 61.5%(8/13) and 64.3%(9/14) in patients treated with orelabrutinib at 50mg, 80mg and 100mg respectively, compared with 35.7%(5/14) in patients treated with placebo, which indicated a trend of dose-dependent improvement.

Among the small cohort of subgroup of patients with SLEDAI-2K≥8 at screening, SRI-4 response occurred in 70%(7/10), 70%(7/10) and 66.7%(6/9) of patients who received orelabrutinib at 50mg, 80mg and 100mg, respectively, compared with 30%(3/10) who received placebo.

A biological signal of reduced proteinuria, anti-dsDNA and IgG, total B cells and increased complements C4 were also observed following orelabrutinib administration.

Professor Zhanguo Li said, "Orelabrutinib was generally well tolerated in patients with SLE. We are encouraged by the preliminary results suggesting trends in efficacy and supporting further studies in longer-term trials and larger cohorts of SLE patients."

More information can be found at EULAR official website.

About Orelabrutinib

Orelabrutinib is a highly selective BTK inhibitor developed by InnoCare for the treatment of cancers and autoimmune diseases.

On Dec. 25 2020, orelabrutinib received conditional approval from the China National Medical Products Administration (NMPA) in two indications: the treatment of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL), and the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL). At the end of 2021, orelabrutinib was included into National Reimbursement Drug list to benefit more lymphoma patients.

In addition to the approved indications, multi-center, multi-indication clinical trials are underway in the US and China with orelabrutinib as monotherapy or in combination therapies.

Orelabrutinib was granted as Breakthrough Therapy Designation for the treatment of r/r MCL by U.S. Food and Drug Administration (FDA).

In addition, orelabrutinib is also being evaluated in global phase II studies for the treatment of Multiple Sclerosis (MS), and clinical trials for the treatment of SLE, Primary Immune Thrombocytopenia (ITP) and Neuromyelitis Optica Spectrum Disorder (NMOSD) in China.

On June 5, 2022 Merus N.V. (Nasdaq: MRUS) ("Merus", "the Company", "we", or "our"), a clinical-stage oncology company developing innovative, full-length multispecific antibodies (Biclonics and Triclonics), reported interim efficacy data as of an April 12, 2022 data cutoff date, from the phase 1/2 eNRGy trial and Early Access Program (EAP) of the bispecific antibody Zeno in patients with NRG1+ cancer presented virtually by Lead Author, Dr. Alison Schram of Memorial Sloan Kettering Cancer Center (MSKCC) at the 2022 ASCO (Free ASCO Whitepaper) Annual meeting (Press release, Merus, JUN 5, 2022, View Source [SID1234615570]).

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"We have made significant progress with enrollment in the eNRGy trial over the past year," said Dr. Andrew Joe, Chief Medical Officer at Merus. "And Zeno continues to demonstrate consistent efficacy in patients with multiple types of NRG1+ cancer. We believe Zeno has the potential to be both first in class and best in class as a tumor agnostic treatment for patients with NRG1+ cancer."

Dr. Schram added, "Zeno has led to durable responses in previously treated NRG1 fusion-positive cancer, with a median duration of response greater than 9 months and more than 25% of those responding continuing at 12 months. Additionally, Zeno has an extremely well tolerated safety profile. There are currently no approved therapies targeting NRG1 fusion-positive cancer and Zeno offers an important, potential new standard of care."

The reported data are from the phase 1/2 eNRGy trial and EAP which are assessing the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancer.

Key findings of the presentation include:

As of April 12, 2022, 110 patients were treated with Zeno
Efficacy was assessed in 79 evaluable patients with measurable disease having the opportunity for 6 months or more follow-up and who met the criteria for the primary analysis population
Median age was 59 years (range of 22-84); 59% were female
Median number of prior lines of systemic therapy was 2, (range of 0-8)
Qualifying NRG1 fusions included 26 distinct fusion partners
ORR per RECIST criteria as assessed by investigator was 34% (95% Cl; 24%-46%) across multiple tumor types
PDAC ORR 42% (8/19)
NSCLC ORR 35% (16/46)
Tumor shrinkage was observed in 70% of patients
Median time to response was 1.8 months, and median duration of exposure was 6.3 months
Median duration of response was 9.1 months, and 20/83 patients were continuing treatment as of the cutoff date
Strong safety profile with a low incidence of Grade 3 or higher treatment-related adverse events, including low rates of severe gastrointestinal and dermatologic toxicity, without clinically significant cardiotoxicity
The full presentation is available on the Publications page of our website.

Company Conference Call and Webcast Information
Merus will hold a conference call and webcast for investors on Sunday, June 5, 2022 at 6:00 p.m. CT to discuss the Zeno clinical data and provide a program update. A replay will be available after the completion of the call in the Investors and Media section of our website for a limited time.

Date: Sunday, June 5, 6:00 p.m. CT
Webcast link: available on our website
Dial-in: Toll-free: 18772601463/ International: 17066435907
Conference ID: 7194538

About the eNRGy Clinical Trial
Merus is currently enrolling patients in the phase 1/2 eNRGy trial to assess the safety and anti-tumor activity of Zeno monotherapy in NRG1+ cancer. The eNRGy trial consists of three cohorts: NRG1+ pancreatic cancer; NRG1+ non-small cell lung cancer; and NRG1+ cancer. Further details, including current trial sites, can be found at www.ClinicalTrials.gov and Merus’ trial website at www.nrg1.com or by calling 1-833-NRG-1234.

About Zeno
Zeno is an antibody-dependent cell-mediated cytotoxicity (ADCC)-enhanced Biclonics that utilizes the Merus Dock & Block mechanism to inhibit the neuregulin/HER3 tumor-signaling pathway in solid tumors with NRG1 gene fusions (NRG1+ cancer). Through its unique mechanism of binding to HER2 and potently blocking the interaction of HER3 with its ligand NRG1 or NRG1-fusion proteins, Zeno has the potential to be particularly effective against NRG1+ cancer. In preclinical studies, Zeno also potently inhibits HER2/HER3 heterodimer formation and tumor growth in models harboring NRG1 fusions.